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M C Gillies

Publications and source records attributed to M C Gillies.

16 recordsLinked to original sources
PubMed1999

A randomized phase II trial of interferon-alpha2b versus 5-fluorouracil after trabeculectomy.

PURPOSE: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-alpha2b (IFN-alpha), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery METHODS: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3-4 weeks postoperatively. Three treatments were compared: (i) IFN-alpha (1 x 10(6)IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-alpha and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. RESULTS: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up,there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-alpha, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100% receiving BOTH. Side effects were similar among the three groups. CONCLUSIONS: These results are consistent with a beneficial effect of IFN-alpha2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments.

Adult↗
PubMed1998

Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone after 18 months of follow up in patients with age-related macular degeneration and subfoveal or juxtafoveal choroidal neovascularization considered unsuitable for laser photocoagulation. METHODS: Thirty eyes of 28 patients, referred from general eye clinics as well as the private clinic of one of the authors to a hospital-based retinal out-patient clinic, were treated with an intravitreal injection of triamcinolone (4 mg). The primary outcome measure was the proportion of eyes with loss of six or more lines on a Bailey-Lovie Chart. The incidence of adverse events associated with treatment was also observed. RESULTS: Of the 20 eyes with initial visual acuity (VA) of 6/60 or better, the vision was maintained (+/-1 Bailey-Lovie lines) in 11 eyes (55%), while six eyes (30%) suffered severe visual loss (six or more lines). The VA improved by five to six lines in three of 10 eyes with initial vision of 3/60 or worse. Three of four eyes receiving a second injection suffered either progressive cataract or elevated intra-ocular pressure (IOP) requiring cataract surgery and/or filtering surgery. One of 26 eyes (3%) receiving a single injection showed progression of cataract and elevation of IOP within 6 weeks of treatment and required anti-glaucoma medication for 6 weeks. Progression of nuclear sclerosis 8-12 months after treatment was observed in six of 26 eyes (23%) receiving a single injection. CONCLUSIONS: The results of the present study suggest that a single intravitreal injection of 4 mg triamcinolone is reasonably well tolerated by the human eye. The rate of development of severe visual loss was less than reported for historical controls. Because the results are preliminary and uncontrolled, the treatment should not be used routinely until its benefit to patients is established by a prospective, randomized controlled study.

Aged↗
PubMed1997

Effect of high glucose on permeability of retinal capillary endothelium in vitro.

PURPOSE: To study the effect of high glucose on the permeability of bovine retinal capillary endothelial cell (BRCEC) monolayers. METHODS: The paracellular permeability of second-passage BRCEC cultured on millipore filters in two chamber transwell inserts was assayed by measuring the peak trans-monolayer electrical resistance and percent equilibration of 14C-inulin 48 hours after it had been added to the luminal chamber. RESULTS: High glucose increased the paracellular permeability of BRCEC monolayers independently of its hypertonic action (5 mM glucose: 154.2 +/- 21.2 and 19.5 +/- 2.4; 30 mM glucose: 134.2 +/- 5.1 [P = 0.01] and 23.5 +/- 2.1 [P = 0.01]; 5 mM glucose + 25 mM mannitol: 168.7 +/- 13.7 ohm.cm2 [P = 0.04] and 19.3% +/- 1.2% 48-hour equilibration of inulin [P = 0.008]). In a separate series of experiments, the authors were unable to show that either aminoguanidine or ponalrestat prevented the effect of high glucose on permeability (30 mM glucose 95.1 +/- 16.7 and 45.4 +/- 5.6; 5 mM glucose: 122.9 +/- 14.2 [P = 0.02] and 36.6 +/- 5.6 [P = 0.001]; 30 mM glucose + aminoguanidine 87.9 +/- 17.5 [P = 0.04] and 75.3 +/- 14.9 [P = 0.6]; 30 mM glucose + ponalrestat 79.9 +/- 12.7 ohm.cm2 [P = 0.1] and 48.2 +/- 2.5% 48-hour equilibration of inulin [P = 0.15]). Ponalrestat did not abrogate the effect of high glucose despite its ability to reduce a high glucose-induced increase in BRCEC intracellular sorbitol levels. CONCLUSIONS: The data are consistent with a role for increased paracellular permeability in breakdown of the blood-retinal barrier in diabetic retinopathy, which appears to be independent of both nonenzymatic glycosylation and the polyol pathway.

Animals↗
PubMed1996

Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy. The Melbourne Excimer Laser Group.

PURPOSE: To determine whether topical interferon alpha 2b (IFN-alpha) prevents corneal haze after excimer laser photorefractive keratectomy (PRK). SETTING: Tertiary referral ophthalmic hospital. METHOD: A prospective, double-blind, placebo-controlled, randomized study of 31 patients was undertaken. After surgery in a single institution, patients received a drop of either a placebo or IFN-alpha (5 x 10(6) IU/ml) four times daily for 4 weeks. The main outcome measures were corneal haze, refraction, and visual acuity. RESULTS: The major side effect of interferon alpha treatment was a significant delay in epithelial healing by a mean of 2 days. The means of the average post-treatment clinical scores for haze in all patients up to 12 months after surgery were 0.46 +/- 0.25 for the IFN-alpha group and 0.64 +/- 0.43 for the placebo group (P = .20). Of patients with a correction of greater than 5.00 diopters (D), the IFN-alpha group had significantly less haze over the course of the study (0.39 +/- 0.23 versus 0.98 +/- 0.50; P = .03). After 12 months, the mean absolute spherical equivalent in the two groups was not significantly different (1.02 +/- 1.13 D versus 1.44 +/- 2.64 D). There was a tendency toward better uncorrected visual acuity in the INF-alpha group (P < .10, Kolmogorov-Smirnov). CONCLUSION: Topical IFN-alpha may merit further investigation as a treatment to reduce corneal haze after excimer laser PRK for corrections greater than 5.00 D.

Administration, Topical↗
PubMed1996

Standards.

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Australia↗
PubMed1995

Interferon-alpha 2b enhances barrier function of bovine retinal microvascular endothelium in vitro.

Increased permeability of the vascular endothelium is a critical part of pathological processes such as inflammation and wound healing. While several cytokines have been shown to increase endothelial permeability, none has been shown to reduce it. We studied the effect of interferon-alpha 2b on the barrier function of bovine retinal capillary endothelial cells in vitro and found that it increased the electrical resistance of the monolayers (treated cells 211 +/- 6 ohm.cm2, untreated 109 +/- 14 ohm.cm2), decreased their permeability to inulin (Pc inulin of untreated cells 0.73 +/- 0.21 x 10(-6) cm/sec, treated 0.31 +/- 0.23 x 10(-6) cm/sec, P = 0.015), and enhanced their morphological differentiation. Interferon-gamma had no effect. No effect of interferon-alpha treatment on the permeability of bovine aortic endothelial cells was found. We conclude that interferon-alpha 2b can enhance the barrier function of retinal microvascular endothelium in vitro. This is consistent with the hypothesis that interferon-alpha is an effector of a mechanism which actively promotes tissue homeostasis and suggests that it might have therapeutic potential in diseases characterized by leakage of the vascular endothelium.

Animals↗
PubMed1995

Electrical resistance and macromolecular permeability of retinal capillary endothelial cells in vitro.

This study was undertaken to examine the ability of retinal capillary endothelial cells to retain blood-retinal barrier properties in vitro. Second passage bovine retinal capillary endothelial cells were grown to confluence on polycarbonate filters in two chamber systems coated with laminin, fibronectin and type IV collagen. The electrical resistances, permeability of 3H-insulin and expression of blood-brain barrier related enzymes by retinal cells was observed and compared with bovine aortic endothelial cells and bovine fibroblasts. The electrical resistance of retinal cells rose over the first week of culture, peaking after 5-9 days in culture. In eleven separate experiments (n = 5 for each experiment) the average peak resistance of retinal endothelial cells ranged from 89.3-186.6 with a mean average of 129.0 ohm.cm2. In one of these experiments, the peak electrical resistance of retinal cells was 149.0 +/- 10.3 compared with 34.8 +/- 6.8 for aortic cells and 37.8 +/- 3.8 ohm.cm2 for fibroblasts. The permeability coefficients of inulin were: retinal cells 0.17 +/- 0.09, aortic cells 3.47 +/- 1.58 (p = 0.015), fibroblasts 3.93 +/- 0.78 (p = 0.002) x 10(-6) cm/sec. Retinal cells expressed significantly higher activities of gamma-glutamyl transpeptidase and alkaline phosphatase than the other cell types. Treatment of the monolayers with the calcium ionophore, A23187, resulted in a reversible increase in permeability as has been described for peripheral vascular endothelium. We conclude that BRCEC retain at least some of their specialised barrier properties in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1993

Treatment of choroidal neovascularisation in age-related macular degeneration with interferon alfa-2a and alfa-2b.

Forty eight eyes of 42 patients with choroidal neovascular membranes and age-related macular degeneration who received three different dose regimens of systemic interferon alfa-2 were studied retrospectively. The response to treatment of 41 eyes of the 37 patients who received at least 4 weeks' treatment was analysed with respect to the change in size of the choroidal neovascular membrane and the visual acuity compared with pretreatment levels. The size of the membrane at the end of the course of treatment had decreased in seven (17%) eyes overall, not changed in 16 (39%), and increased in 18 (44%). At the end of treatment, the visual acuity had improved in seven (17%) eyes, not changed in 27 (66%), and deteriorated in seven (17%). With an average follow up of 10 months after treatment, the visual acuity had deteriorated compared with the pretreatment value in 21 out of 41 (51%) eyes. Vision improved in some fellow eyes with disciform scars. Side effects were common and often severe. The data suggest that one of the major effects of interferon alfa may be to decrease vascular permeability. While further research may identify a place for interferon alfa in the treatment of choroidal neovascularisation, we were unable to demonstrate that the treatment regimens of systemic interferon alfa we used caused a dramatic benefit to patients with exudative age-related macular degeneration.

Aged↗
PubMed1993

High glucose inhibits retinal capillary pericyte contractility in vitro.

PURPOSE: To study the effect of high glucose concentrations on pericyte contractility. METHODS: Bovine retinal capillary pericytes were cultured on silicone rubber sheets, which could be seen to wrinkle when a cell contracted. Cells were grown in glucose, or mannitol, in concentrations ranging from 5 to 40 mMol. Pericyte contractility was expressed as the percentage of cells wrinkling the silicone substratum. Observations were made fortnightly for 8 weeks. RESULTS: Cells grown in glucose exhibited a dose-dependent inhibition of contractility that was significantly greater than that seen with cells grown in mannitol, which were affected to a lesser extent. After returning to normoglycemic conditions for a further 4 weeks, the contractility of cells grown in lower glucose concentrations recovered partially, but cells grown in 40 mMol glucose did not recover at all. Pericyte proliferation was also impaired by the high-glucose growth medium. CONCLUSIONS: Pericyte contractility is inhibited by high glucose concentrations. This is consistent with the hypothesis that increased retinal blood flow may be a factor in the early pathogenesis of diabetic retinopathy.

Animals↗
PubMed1992

A simple method for the in vitro culture of human retinal capillary endothelial cells.

A simple method for the culture of human retinal capillary endothelial cells in vitro is described in this report. Through a process of gentle mechanical disruption and sieving, a sufficient yield of retinal microvessels was obtained from one or two human eyes to allow the culture of endothelial cells in abundance. The cells were factor VIII-positive and demonstrated typical vascular endothelial morphology. Pericyte contamination was prevented by using human platelet-poor serum in primary culture and passaging cells with a low concentration of trypsin. Proliferation assays revealed that the cells grew best in Iscove's modified Dulbecco's modified Eagle's medium with 15% fetal calf serum (FCS). There was no difference in induced proliferation when FCS was compared to human platelet-poor serum. The method seemed to be as good as and much simpler than other recently described techniques. The study of human retinal capillary endothelial cells cultured in this way may shed light on the earliest stages of diabetic retinopathy and other diseases of the retinal microvasculature, particularly AIDS-related retinopathy and radiation retinopathy.

Capillaries↗
PubMed1991

Cytokines, fibrosis and the failure of glaucoma filtration surgery.

Current therapies for the prevention of fibrosis after glaucoma filtering surgery can be effective but often produce unwanted side effects. An understanding of the cellular basis of the fibrotic reaction may lead to better treatments. Wound repair revolves around angiogenesis and the activation of fibroblasts by cytokines. These peptides, a number of which have been described, act together in intricately complicated networks to encourage fibroblast chemotaxis, proliferation and contractility, as well as to stimulate the production of glycosaminoglycans and collagen. Since interferons seem to inhibit many of these responses, they deserve further evaluation in the treatment of ocular fibrosis.

Cytokines↗
PubMed1990

The evolution of function and response to arginine challenge and pregnancy of portally and systemically placed islet cell grafts in streptozotocin diabetic mice.

Mice made diabetic with streptozotocin received organ cultured fetal islet cell grafts in the portal (PG) or systemic (SG) vascular beds in order to determine whether portal delivery of insulin is an important consideration in graft placement. Grafts were established more quickly in SG mice as shown by body weight and blood glucose estimations. Intraperitoneal arginine was found to be a stronger insulin secretagogue than intravenous glucose with the doses used when serum insulin was measured 5 minutes after injection. Glucose response to an arginine challenge was initially abnormal in both groups of mice, but was identical to normal controls 4 months after transplantation, showing that engraftment is a gradual process. Mice were then mated and their response to the chronic glycemic stress of pregnancy was noted. PG and SG mice had normal fertility rates in contrast to untreated diabetics, none of which became pregnant. Offspring were normal with respect to litter size, body weight, malformation rate, and pancreatic insulin content compared with historical controls. PG and SG mothers behaved normally during pregnancy, with the exception of a raised glycosylated hemoglobin level at day 19.5 gestation (5.5% and 5.5% v 3.7%, P less than .01). We were, therefore, unable to detect any difference between portally and systemically placed islet grafts.

Animals↗
PubMed1990

The prevention of diabetic retinal and renal basement membrane thickening in mice by islet cell allografts.

The effect of fetal islet cell allografts on retinal capillary (RCBMT) and glomerular (GBMT) basement membrane thickening in diabetic mice was studied, as well as the effect of diabetes on the anterior lens capsule and the inner lamina of Descemet's membrane. CBA mice rendered diabetic with streptozotocin received fetal pancreatic islet cell grafts from C3H and BALB/c donors four weeks after induction of diabetes with an additional late transplant group receiving C3H grafts after six months of diabetes. After 12 months animals with successful grafts were examined for RCBMT along with untreated diabetics (UD, n = 4) and normals (N, n = 9). Untreated diabetics had significantly increased RCBMT (167.1 +/- 12.1 vs 129.2 +/- 24.3 nm, p = 0.05) and GBMT (278 +/- 11 vs 248 +/- 6 nm, p = 0.004) compared to normals. All graft recipients had RCBMT similar to normal and significantly less than untreated diabetics: BALB/c (n = 7), 123.8 +/- 21.0, p = 0.02; C3h early (n = 5), 126.6 +/- 21.7, p = 0.05; C3H late (n = 4), 134.4 +/- 16.9, p = 0.03. The same was true for GBMT; 250 +/- 10 nm, p = 0.02 for BALB/c recipients, 250 +/- 8 nm, p = 0.04 for early and 255 +/- 9 nm, p = 0.02 for late C3H recipients. GMBT in six month biopsies of normals and prospective late graft recipients were well below these levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of topical interferon-alpha 2b on corneal haze after excimer laser photorefractive keratectomy in rabbits.

BACKGROUND: Anterior corneal stromal keratocytes are activated by excimer laser photorefractive keratectomy resulting in haze with healing of the ablated area. In some eyes, this causes a visible haze or scar on the cornea, and an unpredictable regression of the myopic correction following refractive ablations. METHODS: Following a 6.00-diopter excimer laser photorefractive keratectomy to both eyes, 16 rabbits were treated for 5 weeks with interferon-alpha 2b drops four times a day to one eye only. Eight of these rabbits were treated with dexamethasone drops four times a day to both eyes. Using a standard grading scale for haze, the corneas were examined and the haze graded weekly. RESULTS: The observed corneal haze was significantly reduced in the treated eyes by the application of topical interferon-alpha 2b drops (p = .004), and topical dexamethasone drops (p < .001). Topical dexamethasone also produced less haze in combination with interferon-alpha 2b than when used alone (p = .035). There was continuing resolution of the corneal haze in those rabbits observed for 7 weeks after the cessation of the drops. Topical interferon-alpha therapy was not toxic to the rabbit eye and was not associated with delayed reepithelialization after the laser procedure. CONCLUSION: Topical interferon-alpha 2b appears to reduce the corneal haze produced by excimer laser photorefractive keratectomy in rabbits.

Administration, Topical↗